Myeloproliferative neoplasms

The Philadelphia-negative myeloproliferative neoplasms, polycythaemia vera, essential thrombocythaemia and myelofibrosis, are uncommon clonal haematological malignancies that are generally diagnosed from late middle age onwards, although they may occur in children and young adults. Each of these disorders has unique features but their clinical courses have similarities, including thrombosis, haemorrhage, a tendency for progressive myelofibrosis and the development of acute myeloid leukaemia. Myelofibrosis is associated with a much poorer prognosis than the other conditions, and death, usually due to progressive bone marrow failure or leukaemia. Recently, a mutation at position 617 in exon 14 of the JAK2 gene (JAK2 V617F) has been identified in the majority of patients with polycythaemia vera and half of those with essential thrombocythaemia or myelofibrosis. This has improved diagnostic pathways, but challenges their current classification as separate entities. Current treatment for these patients involves aggressive management of thrombotic risk factors, aspirin for most patients unless contraindicated, and cytoreductive agents such as hydroxycarbamide for patients at high risk of thrombosis. A new class of drugs, JAK inhibitors, has proven to be effective for symptomatic myelofibrosis and the first of these agents has recently been licensed.